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Expanding the genetic landscape of Rett syndrome to include lysine acetyltransferase 6A(KAT6A)

Journal of Genetics and Genomics 2020年第10期47卷 650-654页

作者： Simranpreet Kaur Nicole J.Van Bergen Bruria Ben-Zeev Emanuela Leonardi Tiong Y.Tan David Coman Benjamin Kamien Susan M.White Miya St John Dean Phelan Kristin Rigbye Sze Chern Lim Michelle C.Torres melanie marty Elena Savva Teresa Zhao Sean Massey Alessandra Murgia Wendy A.Gold John Christodoulou Brain and Mitochondrial Research Group Murdoch Children's Research InstituteMelbourneAustralia Department of Paediatrics University of MelbourneMelbourneAustralia Paediatric Neurology Institute The Edmond and Lily Safra Paediatric HospitalSheba Medical CenterTel HaShomerIsrael Sackler School of Medicine Tel Aviv UniversityIsrael Molecular Genetics of Neurodevelopment Department of Woman and Child HealthUniversity of PadovaItaly Fondazione Istituto di Ricerca Pediatrica(IRP) Citta della SperanzaPadovaItaly Victorian Clinical Genetics Services Murdoch Children's Research InstituteMelbourneAustralia Department of Paediatrics The Wesley HospitalBrisbaneBrisbaneAustralia Queensland Children's Hospital BrisbaneAustralia School of Medicine University of QueenslandBrisbaneAustralia Genetic Services of Western Australia Western AustraliaAustralia Faculty of Health and Medical Sciences University of Western AustraliaAustralia Speech and Language Murdoch Children's Research InstituteParkvilleVictoriaAustralia Department of Audiology and Speech Pathology University of MelbourneParkvilleVictoriaAustralia The University of Sydney School of Medical Sciences and Discipline of Child and Adolescent HealthFaculty of Medicine and HealthSydneyAustralia Molecular Neurobiology Lab Kids ResearchWestmead Children's HospitalWestmeadSydneyAustralia Kids Neuroscience Centre Kids ResearchChildren's Hospital at WestmeadWestmeadSydneyAustralia

Pathogenic variants in methyl-Cp G protein 2(MECP2;OMIM300005)result in an X-linked,severe,and progressive epigenetic disorder,Rett syndrome(RTT,OMIM:312750),that predominantly affects females(Rett,1966).Using Neul’s revised diagnostic criteria,affected individuals can be clinically classified as classic or atypical RTT(Neul et al.,2010).

关键词： Rett al. landscape

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Hierarchical mechanical behavior of cobalt supracrystals related to nanocrystallinity

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Nano Research 2015年第11期8卷 3480-3487页

作者： melanie Gauvin Sorbonne Universites UPMC Univ Paris 06 UMR 8233 MONARIS Paris F-75005 France CNRS UMR 8233 MONARIS Paris F-75005 France CEA/IRAMIS CEA Saclay Gif-sur-Yvette 91191 France

Here, we report on hierarchical mechanical behavior of 500-nm-thick Conanocrystal 3D superlattices （supracrystals） induced by either the crystalline structure （nanocrystallinity） or the length of the coating agent of Co nanocrystals. Increasing the nanocrystal shape anisotropy of Co nanocrystals through the control of their nanocrystallinities induces a higher level of ordering with both translational and orientational alignment of nanocrystals within the supracrystals. The hierarchy in ordering at various scales, i.e., from the atomic lattice within the nanocrystals to the nanocrystal superlattices within supracrystals, is correlated with marked changes in the Young＇s modulus of supracrystals： From 0.7 ±0.4 to 1.7 ±0.5 and to 6.6 ±1.5 GPa as the crystalline structure of Co nanoparticles changes from amorphous-Co to ε-Co and to hexagonal compact packing （hcp）-Co, respectively. Moreover, for supracrystals of 7 nm amorphous Co nanoparticles, the Young＇s modulus decreases by one order of magnitude from 0.7 ±0.4 to 0.08 ±0.03 GPa upon reducing the alkyl chain length of the ligands coating the Co nanoparticles from C18 （oleic acid） to C12 （lauric acid）. The hierarchical mechanical behavior is rationalized using a dimensional model of the stress-strain relationship in supracrystals.

关键词： supracrystal crystallinity anisotropy orientational alignment mechanical properties

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Do black-furred animals compensate for high solar absorption with smaller hairs？ A test with a polymorphic squirrel species

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Current Zoology 2011年第6期57卷 731-736页

作者： melanie A. FRATTO Andrew K. DAVIS Odum School of Ecology The University of Georgia Athens GA USA 30602

In polymorphic mammalian species that display multiple color forms, those with dark, or melanic pelage would be prone to overheating, especially if they live in warm climates, because their fur absorbs solar energy at a higher rate. However, experimental studies indicate that certain physical properties of fur of dark individuals appear to prevent, or minimize heat stress, although it is not clear what properties do so. Here, we tested the possibility that black-furred individuals simply have shorter or thinner hair fibers, which would create a lighter （in terms of weight） coat or one that allows greater air flow for evaporative coo- ling. We examined museum specimens of eastern fox squirrels Sciurus niger, a species native to the United States and one that displays brown, grey or all-black pelage color, and used image analysis procedures to quantify hairs from the dorsal surface and tail. From examination of 43 specimens （19 brown, 9 black and 15 grey）, and 1,720 hairs, we found no significant difference in hair lengths across color morphs, but significant differences in hair fiber widths. Black squirrels had thinner body hairs than other forms （7% thinner）, but thicker tail hairs （9% thicker） than the others. Given that the dorsal surface would be directly exposed to solar radiation, we interpret this to be an adaptation to prevent heat stress during the day. The thicker tail hairs may be an adapta- tion for nighttime thermoregulation, since squirrels sleep with their tails wrapped around their bodies. These results add to a growing literature body of the functional significance of mammalian pelage [Current Zoology 57 （6）： 731-736, 2011].

关键词： Polymorphism Melanism Fox squirrels Sciurus niger Heat stress Hair morphology

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Aggregation and mating success of Capnodis tenebrionis （Coleoptera： Buprestidae）

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Insect Science 2014年第2期21卷 203-212页

作者： Carmelo Peter Bonsignore Theresa melanie Jones Dipartimento Patrimonio Architettonico e Urbanistico PAU Laboratorio di Entomologia ed Ecologia Applicata Universita Mediterranea di Reggio Calabria Safita Mefissari Reggio Calabria Italy Department of Zoology The University of Melbourne 3010 Victoria Austrafia

An understanding of the relative importance of extrinsic and intrinsic factors in determining the potential distribution and mating success of individuals is critical for the successful monitoring and management of pest species. Using a combination of field observations and a caged field experiment, we explored the roles of environmental and individual variation on the formation of mating aggregations and mating success in the buprestid beetle Capnodis tenebrionis （Linnaeus, 1767）, a pest species of stone fruit trees. Our field observations revealed that the formation of aggregations is influenced by a range of environmental factors including temperature, photoperiod, and population density. However, aggregations were not at random and were more likely to occur on the section of the plant with highest incidence of solar radiation and thus higher temperatures. Data from our experiment with caged beetles in the field further indicate that the reproductive behavior of this species varies with temperature. The probability of a successful mating occurring was also positively related to both male and female size. Females of C. tenebrionis mate several times over a 4-h period, but generally not with the same male. Information obtained from these studies is useful to define the most appropriate time for pest control, especially adopting strategies that interfere with reproduction.

关键词： body size Buprestidae Capnodis Coleoptera mating success sexualselection

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New Insight in Ethylene Signaling： Autokinase Activity of ETR1 Modulates the Interaction of Receptors and EIN2

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Molecular Plant 2010年第5期3卷 882-889页

作者： melanie M.A. Bisson Georg Groth Heinrich-Heine Universitat Dusseldorf Biochemie der Pflanzen Universitatsstr. 1 40225 Dosseldorf Germany

Ethylene insensitive 2 （EIN2）, an integral membrane protein of the ER network, has been identified as the central regulator of the ethylene signaling pathway. Still, the mechanism by which the ethylene signal is transferred from the receptors to EIN2 has not been solved yet. Here, we show that protein phosphorylation is a key mechanism to control the interaction of EIN2 and the receptors. In vivo and in vitro fluorescence studies reveal that the kinase domain of the receptors is essential for the interaction. Cyanide, an ethylene agonist, which is known to reduce auto-phosphorylation of the ethylene receptor ethylene resistant 1 （ETR1） or a mutation in the kinase domain of ETR1 that prevents autophosphorylation （H353A）, increases the affinity of the receptors for EIN2. On the other hand, mimicking permanent auto-phosphorylation of ETR1 as in the mutant H353E releases the EiN2-ETR1 interaction from the control by the plant hormone. Based on our data, we propose a novel model on the integration of EIN2 in the ethylene signaling cascade.

关键词： Membrane biochemistry protein phosphorylation/dephosphorylation receptors signal transduction membrane proteins ethylene protein-protein interaction.

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Targeting Plant Ethylene Responses by Controlling Essential Protein-Protein Interactions in the Ethylene Pathway

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Molecular Plant 2015年第8期8卷 1165-1174页

作者： melanie M.A. Bisson Georg Groth Institute of Biochemical Plant Physiology Heinrich-Heine University Dusseldorf D-40204 Dusseldorf Germany

The gaseous plant hormone ethylene regulates many processes of high agronomic relevance throughout the life span of plants. A central element in ethylene signaling is the endoplasmic reticulum （ER）-Iocalized membrane protein ETHYLENE INSENSITIVE2 （EIN2）. Recent studies indicate that in response to ethylene, the extra-membranous C-terminal end of EIN2 is proteolytically processed and translocated from the ER to the nucleus. Here, we report that the conserved nuclear localization signal （NLS） mediating nuclear import of the EIN2 C-terminus provides an important domain for complex formation with ethylene receptor ETHYLENE RESPONSE1 （ETR1）. EIN2 lacking the NLS domain shows strongly reduced affinity for the receptor. Interaction of EIN2 and ETR1 is also blocked by a synthetic peptide of the NLS motif. The corre- sponding peptide substantially reduces ethylene responses in planta. Our results uncover a novel mecha- nism and type of inhibitor interfering with ethylene signal transduction and ethylene responses in plants. Disruption of essential protein-protein interactions in the ethylene signaling pathway as shown in our study for the EIN2-ETR1 complex has the potential to guide the development of innovative ethylene antagonists for modern agriculture and horticulture.

关键词： fruit ripening ethylene responses peptide protein-protein interactions inhibitor

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Effects of a municipal effluent on the freshwater mussel Elliptio complanata following challenge with Vibrio anguillarum

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Journal of Environmental Sciences 2015年第11期27卷 91-99页

作者： Gagne Francois Douville melanie Fortier Marlene Fournier Michel Aquatic Contaminants Research Division Water Science and Technology INRS-Institut Armand-Frappier

The purpose of this study was to examine the cumulative effects of exposure to a pathogenic bacteria and municipal effluent in the freshwater mussel Elliptio complanata. Mussels were exposed to increasing concentrations of an ozone-treated effluent at 15°C for 7 days. A sub-group of mussels was inoculated with Vibrio anguillarum and exposed to the same conditions as *** the exposure period, mussels were collected to assess hemocyte count and viability,immunocompetence（phagocytosis and nitrite production）, oxidative stress/inflammation（cyclooxygenase and lipid peroxidation） and oxygen radical/xenobiotic scavenging activity（metallothioniens, glutathione S-transferase）. The results showed that mussels exposed to municipal effluent had increased hemocyte counts, phagocytosis, nitrites, lipid peroxidation and metallothioneins. In the inoculated mussels, the same responses were observed, in addition to cyclooxygenase and glutathione S-transferase activities. Multivariate analyses revealed that（1）the response pattern changed with effluent concentration, where increased responses observed at low effluent concentrations（〉10%, V/V） were attenuated at higher effluent concentrations,（2）the effluent produced more pronounced changes in lipid peroxidation, metallothionein and hemocyte viability, and（3） the simultaneous presence of V. anguillarum led to more important changes in hemocyte count and viability and nitrite levels. In conclusion, the presence of *** could alter the response of mussels to municipal effluent, which could lead to increased inflammation in mussels.

关键词： Elliptio complanata Immunocompetence Oxidative stress Inflammation Vibrio anguillarum

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Taking China’s anticorruption campaign seriously

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Economic and Political Studies 2016年第1期4卷 3-18页

作者： melanie Manion Department of Political Science Duke UniversityDurhamUSA

This article draws on a rich empirical literature on comparative corruption and rich theoretical literatures on the related topics ofinstitutions and credible commitment to analyze China’s newestanticorruption campaign, ongoing today. It argues that the campaign differs notably from previous efforts. In addition to its mostobvious features of longer duration and higher reach, the campaign has significantly changed the structure of Party and government incentives so as to reduce bureaucratic opportunities forcorruption and structural obstacles to anticorruption *** features constitute important steps toward anticorruptioninstitutionalisation and credible commitment to good *** article concludes by proposing some strategic policy choicesto promote and protect anticorruption gains.

关键词： Anticorruption campaigns corruption credible commitment

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Advances of nanotechnologies for hydraulic fracturing of coal seam gas reservoirs:potential applications and some limitations in Australia

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International Journal of Coal Science & Technology 2022年第2期9卷 1-18页

作者： Hannah Marsden Sudeshna Basu Alberto Striolo melanie MacGregor Department of Chemical Engineering University College LondonLondon WC1E 7JEUK Future Industries Institute University of South AustraliaMawson Lakes BvdMawson LakesSA 5195Australia Department of Earth Sciences University College LondonLondon WC1E 6BSUK School of Chemical Biological and Materials EngineeringUniversity of OklahomaNormanOK 73019USA Flinders Institute for Nanoscale Science&Technology College of Science and EngineeringFlinders UniversityBedford ParkSA 5042Australia

Some of the most promising potential applications of nanotechnology to hydraulic fracturing of coal seam gas(CSG)are reviewed with a focus on Australian CSG *** propitious applications were identifed:(1)Nanoparticle enhanced viscoelastic surfactants(VES)fracturing fuids to prevent fuid loss by up to 30%,made possible by the formation of pseudo-flter cakes and reducing the viscosity of the VES ***,there is no requirement of clay control additives or biocides.(2)Nano-proppants to extend fracture networks and reduce proppant embedment by introducing them prior to the emplacement of larger *** Ash nanoparticles can be particularly efective because of their high sphericity and mechanical strength.(3)Nanoparticle-coated proppants,to mitigate the migration of particle fnes by restricting them close to their source by adsorption,with MgO being the most *** use of nanotechnology in hydraulic fracturing applications is currently hindered due to a discordant regulatory environment compounded by the cost of the nanoparticles themselves,as well as,a lack of feld data to validate the technology under real downhole *** the necessary feld tests are unlikely to be conducted for as long as abundant natural gas is available,exploratory studies could pave the way for future applications.

关键词： Coal bed methane Nanoparticles Fracturing fuids Proppant Natural gas

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Targeting the EGF receptor family in non-small cell lung cancerincreased complexity and future perspectives

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Cancer Biology & Medicine 2022年第11期19卷 1543-1564页

作者： Tobias Boch Jens Kohler melanie Janning Sonja Loges DKFZ-Hector Cancer Institute at the University Medical Center Mannheim Mannheim 68135Germany Division of Personalized Medical Oncology(A420) German Cancer Research Center(DKFZ)Heidelberg 69120Germany Department of Personalized Oncology University Medical Center MannheimMedical Faculty MannheimHeidelberg UniversityMannheim 68135Germany

Lung cancer remains the leading cause of cancer-associated mortality worldwide,but with the emergence of oncogene targeted therapies,treatment options have tremendously *** to their biological relevance,members of the ERBB receptor family,including the EGF receptor(EGFR),HER2,HER3 and HER4,are among the best studied oncogenic *** EGFR mutations are frequently observed in non-small cell lung cancer(NSCLC),and small molecule tyrosine kinase inhibitors(TKIs)are the established first line treatment option for patients whose tumors bear"typical/classical"EGFR mutations(exon 19 deletions,L858R point mutations).Additionally,new TKIs are rapidly evolving with better efficacy to overcome primary and secondary treatment resistance(e.g.,that due to T790M or C797S resistance mutations).Some atypical EGFR mutations,such as the most frequent exon 20 insertions,exhibit relative resistance to earlier generation TKIs through steric *** this subgroup,newer TKIs,such as mobocertinib and the bi-specific antibody amivantamab have recently been approved,whereas less frequent atypical EGFR mutations remain *** contrast to EGFR,HER2 has long remained a challenging target,but better structural understanding has led to the development of newer generations of *** recent FDA approval of the antibody-drug conjugate trastuzumab-deruxtecan for pretreated patients with HER2 mutant NSCLC has been an important therapeutic ***3 and HER4 also exert oncogenic potential,and targeted treatment approaches are being developed,particularly for ***,strategies to inhibit the oncogenic function of ERBB receptors in NSCLC are currently evolving at an unprecedented pace;therefore,this review summarizes current treatment standards and discusses the outlook for future developments.

关键词： Oncology NSCLC EGFR HER2 HER3 HER4

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